Composite hemangioendothelioma in the cervical spine with kaposiform hemangioendothelioma features in an elderly patient: a case report

Background Composite hemangioendothelioma (CHE) is an intermediate group of tumors with features between hemangioma and angiosarcoma both histologically and biologically. CHE is predominant in young and middle-aged adults, but very infrequently affects the spine. We describe the case of primary CHE in the cervical spine exhibiting kaposiform hemangioendothelioma (KHE)-like components that was associated with cervical myelopathy with vertebral body destruction in an elderly woman. We retrospectively reviewed the case of a primary cervical spinal tumor, diagnosed as CHE with KHE-like components in pathological findings, associated with cervical myelopathy and cervical vertebral body destruction. Case presentation An 80-year-old woman presented with progressive cervical myelopathy caused by a cervical spine tumor. Preoperative cervical MRI revealed a neoplastic lesion invading the cervical spine that strongly compressed the spinal cord, causing right upper-limb paralysis. We performed partial tumor resection along with posterior decompression and fixation. Postoperatively, pathological findings showed that the tumor was CHE with KHE-like features. Following radiotherapy, no recurrences have been observed in 21 months. Conclusions This is the first report of CHE with features of KHE in the spine of an elderly patient. Posterior decompression and fusion of the cervical spine and subsequent radiotherapy resulted in a good outcome.


Background
Composite hemangioendotherioma (CHE) is a rare intermediate endothelial tumor first described by Nayler et al. [1]. In the 2020 World Health Organization classification of Tumors of Soft Tissue and Bone, CHE was defined as a locally aggressive, rarely metastasizing vascular neoplasm containing a mixture of histologically distinct benign and malignant components [2]. The most common site of CHE is the soft tissues of the extremities or trunk, with spinal cases rarely reported [3][4][5]. The present patient is the oldest diagnosed case of CHE occurring in the spine.

Case presentation
An 80-year-old woman presented to our hospital with the chief complaints of difficulty in raising her right upper limb, progressive dyskinesia, and gait disorder. She had been experiencing neck pain for approximately 2 years and numbness in her extremities for roughly a year before her visit, both of which had progressed remarkably prior to presentation. She could manage to walk unassisted for less than 100 m.
Regarding limb strength, muscle weakness (manual muscle testing [MMT] score: 3) was observed in the entire right upper limb. Her strength in the remaining limbs was normal. Hypesthesia was noted throughout the upper and lower limbs. Her deep tendon reflexes were increased bilaterally in all limbs, with positive Hoffman's and Wartenberg's signs. Her preoperative Japanese Orthopaedic Association (JOA) score was 8.5 points. Radiographs and cervical contrast CT revealed osteolytic lesions in C3-7. A mass was seen to extend into the spinal canal from within the vertebrae, compressing the cervical spinal cord from the right side. The mass was stained in the early contrast phase and showed an internal low-density area (Figs. 1 and 2a-c). MRI detected a mass with the same signal profile as bone from within the C3-7 vertebrae to outside of the vertebral bodies, and the cervical spinal cord was compressed from the right side at the same levels (Fig. 2d, e). Blood tests disclosed no thrombocytopenia, anemia, or coagulation abnormalities. Her inflammatory response was normal. Blood cultures and various tumor markers were negative. A percutaneous vertebral biopsy showed culture negativity and no neoplastic lesions. We ultimately performed posterior decompression and fixation of C2-T1 with tumor reduction to improve her cervical myelopathy symptoms (Fig. 3).
In histopathological analysis, the resected specimen exhibited various and complex proliferating patterns of vasoforming cells in low-magnification images, with most areas showing a combination of solid and vasodilated proliferating patterns (Fig. 4a). In solid areas, numerous vascular cavities had been formed by atypical cells, including epithelioid cells with infrequent  (Fig. 4b). In the periphery, irregular nodules had infiltrated into the adjacent muscular and fattyfibrous tissue (Fig. 4c). The nodules had a slit-like structure with spindle cells (Fig. 4d). Several nodules contained epithelioid cell proliferation (Fig. 4e) that clearly showed ERG (Fig. 4f ), CD31, and CD34, but not D2-40, immunopositivity, which were surrounded by cells positive for the pericytic markers myo1B (Fig. 4g), CD146, and SMA. The proliferating cells were negative for markers of epithelioid hemangioendothelioma, including CAMTA1, TFE3, and FOSB (data not shown). The Ki-67 labelling index was calculated  Postoperatively, we commenced radiation therapy (50 Gy/25 Fr). At 21 months after surgery, her right upper extremity muscle strength had improved (MMT score: 5), she had no motor or sensory deficits in her extremities, and was able to walk steadily. Her JOA score improved to 17 points, with no signs recurrence in imaging findings (Fig. 5).

Discussion and conclusion
To the best of our knowledge, this case is the first of spondylogenic CHE in an elderly woman. Although CHE commonly occurs in the skin and soft tissues of the extremities and trunk, it has also been reported in the periaortic region, pulmonary vein, liver, spleen, pancreas, lung, and right atrium [4,[6][7][8]. CHE generally afflicts young to middle-aged adults but can occur at any age [4,7,9]. The diagnosis of the present case was difficult since reports of CHE in the spine and bones are very rare. However, the combination of several pathological features led to the identification and successful treatment of CHE.
The diagnosis of CHE is challenging. Most cases present with various histological features, such as hemangioma, retiform HE, epithelioid HE, spindle HE, and low-grade angiosarcoma [1]. Shin et al. reported that the mean Ki-67 index was 4.6% for all hemangiomas and 38.1% for all angiosarcomas, with 15.0-17.5% as the cutoff value to distinguish between hemangioma and lowgrade angiosarcoma [10]. In our patient's specimen, most areas showed a combination of solid and vasodilated proliferating patterns with a variety of vascular cavities formed by atypical cells, including epithelioid cells with infrequent mitosis and a relatively low Ki-67 index (16.1%), as evidence of angiosarcoma. These findings supported our diagnosis of the partial presence of lowgrade angiosarcoma-like features. Although the spindle cell component in CHE is not rare [1,2], the patient had solid and irregular nodules infiltrating into the adjacent muscular and fatty-fibrous tissue in the periphery. Some nodules included epithelioid endothelial cell proliferation surrounded by myo1B-, CD146-, and SMA-positive pericytes, which were considered as an epithelioid hemangiomatous component. As Lyons documented that KHE comprises scattered glomeruloid nodules containing epithelioid endothelium and αSMA-positive pericytes in addition to spindle cell proliferation [11], our case also partially resembled KHE. Considering the complex morphology of proliferating cells, our patient was diagnosed as having CHE with KHE-like features.
A review of the literature identified a total of 52 patients with CHE (mean age: 42.5 years) reported in the English language, including a 48-year-old woman with CHE in the spine [12]. Most patients underwent surgical treatment. Radiotherapy, chemotherapy, electron beam irradiation, interferon-α 2b, and thalidomide have also been described as effective for CHE with or without resection, although are less common than surgery [12][13][14][15][16][17]. Since CHE in the spine or bones is rare, there remains no consensus on its treatment [13,14]. Dong et al. described a case of a 56-year-old man with CHE in the manubrium sterni, in which lesion resection was performed [3]. Gok et al. reported a case of CHE in paravertebral muscle in a 54-year-old man also treated by excision only [18]. In contrast, Mani et al. described a case of CHE in the calcaneus, distal femur, proximal tibia, and patella of the left leg, as well as a case of CHE in the left fibula and foot, which were treated with radical resection by above-knee and below-knee amputation, respectively [5]. Cheuk et al. encountered a case of CHE in paravertebral soft tissue that was prone to recurrence after resection [19].
Mahmoudizad et al. reported that radiotherapy for CHE on the scalp resulted in tumor shrinkage [13]. Sakamoto et al. performed surgical resection of CHE in the foot and radiotherapy alone for CHE in the lower extremity arteries. The lower-extremity CHE shrunk in size and had not recurred at 2.5 years [14]. In the present case, the tumor could not be completely resected, which necessitated postoperative radiation therapy. No evidence of tumor re-growth was seen at the most recent follow-up.